Heme and lipid peroxides in hemoglobin-modified low-density lipoprotein mediate cell survival and adaptation to oxidative stress

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1732-1739 ◽  
Author(s):  
Liana Asatryan ◽  
Ouliana Ziouzenkova ◽  
Roger Duncan ◽  
Alex Sevanian
Keyword(s):  
Oxidative Stress ◽  
Cell Survival ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxides ◽  
Ldl Oxidation ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
Atherosclerotic Lesions ◽  
Ldl Particles

AbstractLow-density lipoprotein (LDL) oxidation mediated by a variety of catalysts in atherosclerotic lesions plays a crucial role in the genesis and evolution of atherosclerotic plaques. In this study we focused on oxidative properties of hemoglobin (Hb)–modified LDL because Hb is present in atherosclerotic lesions. Under low oxygen tensions Hb was previously found to modify apolipoprotein B100 with covalent binding of Hb fragments and formation of electronegative LDL particles (LDL–). Here we show that HbLDL is highly susceptible to oxidation, but is not cytotoxic to vascular cells, as was found for LDL– isolated from human plasma. HbLDL and LDL– have similar levels of oxidized lipid products and low uptake rates; however, the virtual absence of HbLDL-induced toxicity depends on a marked adaptive oxidative stress response. This was evidenced by a time- and dose-dependent induction of heme oxygenase (HO-1). Cell survival was significantly decreased in the presence of HO-1 inhibitor, tin protoporphyrin (SnPPIX). HO-1 induction by HbLDL increased resistance of cells to toxic doses of hemin or t-BuOOH. The high sensitivity to oxidation and HO-1 induction was largely dependent on lipid hydroperoxides and heme associated with HbLDL. Reduction of pre-existing lipid peroxides using ebselen delayed HbLDL kinetics and inhibited HO-1 induction. Moreover, heme inactivation or its degradation inhibited HO-1 induction and provided an additive inhibitory effect to ebselen. We conclude that Hb-catalyzed reactions may modulate vascular cell survival and oxidative stress adaptation due to the presence of peroxides and heme, thus providing a possible mechanism for the evolution of atherosclerotic and hemorrhagic lesions.

scholarly journals When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

1999 ◽  
Vol 340 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Marco BAGNATI ◽  
Cristina PERUGINI ◽  
Cristiana CAU ◽  
Roberta BORDONE ◽  
Emanuele ALBANO ◽  
...  
Keyword(s):  
Uric Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxides ◽  
Water Soluble ◽  
Ldl Oxidation ◽  
Lag Phase ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
Oxidant Effect

The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with α-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of α-tocopherol was not a prerequisite for unmasking the pro-oxidant activity of uric acid, since this became apparent even when α-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous α-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions.

scholarly journals The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation

1993 ◽  
Vol 294 (3) ◽  
pp. 829-834 ◽  
Author(s):  
M I Mackness ◽  
C Abbott ◽  
S Arrol ◽  
P N Durrington
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Antioxidant Vitamins ◽  
Ldl Oxidation ◽  
Low Density ◽  
Conjugated Diene ◽  
Peroxide Formation

1. The oxidation of low-density lipoprotein (LDL) is believed to play a central role in atherogenesis. We have compared the effect of antioxidant vitamins and high-density lipoprotein (HDL) on the Cu(2+)-catalysed oxidation of LDL. 2. Antioxidant vitamin supplementation significantly reduced conjugated diene formation but did not affect the formation of lipid peroxides. 3. Conversely, HDL did not affect conjugated diene formation but inhibited the formation of lipid peroxides by up to 90%. 4. The inhibition by HDL of lipid peroxide formation in oxidized LDL was dependent on the concentration of HDL and was not due to HDL chelating Cu2+. 5. Large interindividual variations in the inhibition of lipid peroxide formation by autologous HDL were evident, which were related to the rate of lipid peroxide generation in the LDL. 6. We conclude that HDL is a powerful antioxidant or more probably inhibitor of LDL oxidation in vitro and may play an important role in vivo in preventing atherosclerosis by inhibiting LDL oxidation in the artery wall.

scholarly journals Low-density lipoprotein is the major carrier of lipid hydroperoxides in plasma. Relevance to determination of total plasma lipid hydroperoxide concentrations

1996 ◽  
Vol 313 (3) ◽  
pp. 781-786 ◽  
Author(s):  
Jaffar NOUROOZ-ZADEH ◽  
Jarad TAJADDINI-SARMADI ◽  
K. L. Eddie LING ◽  
Simon P. WOLFF
Keyword(s):  
Total Lipid ◽  
Xylenol Orange ◽  
Low Density Lipoprotein ◽  
Lipid Hydroperoxide ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Lipid Hydroperoxides ◽  
Very Low Density Lipoprotein ◽  
Low Density

High-density lipoprotein (HDL) has been proposed as the principal carrier of hydroperoxides in plasma, based upon data gathered with an HPLC-chemiluminescence technique. To test this hypothesis we have measured total lipid hydroperoxides in native plasma using the ferrous oxidation in Xylenol Orange (FOX) assay and then fractionated plasma into very-low-density lipoprotein, low-density lipoprotein (LDL) and HDL fractions. Hydroperoxides were found to accumulate principally (more than 65%) in LDL, as judged by hydroperoxide content per amount of protein or cholesterol, or expressed as a proportion of total hydroperoxide in plasma. Plasma was also incubated at 37 °C in the presence and absence of 2,2´-azo-bis-(2-amidinopropane) hydrochloride (AAPH), an azo-initiator of lipid peroxidation. The majority of hydroperoxides generated in plasma were recovered in the LDL fraction. Furthermore, when isolated lipoproteins were subject to oxidation initiated by AAPH, very-low-density lipoprotein and LDL showed the greatest propensity for hydroperoxide accumulation, whereas HDL seemed relatively resistant. Estimates for plasma and LDL peroxidation based upon techniques which measure total lipid hydroperoxides suggest that levels of hydroperoxides in plasma and LDL are far higher than that those estimates generated by ostensibly more selective techniques. Higher levels of hydroperoxides in LDL than those reported by HPLC-chemiluminescence also seem in greater accordance with other available data concerning LDL oxidation.

scholarly journals Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions

2002 ◽  
Vol 366 (1) ◽  
pp. 195-201 ◽  
Author(s):  
Tao FU ◽  
Jayme BORENSZTAJN
Keyword(s):  
Immunofluorescence Microscopy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Calcium Dependent ◽  
Reactive Protein ◽  
Atherosclerotic Lesions ◽  
Ldl Particles

Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL—CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.

Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk?

2009 ◽  
Vol 47 (2) ◽  
Author(s):  
Eline Verhoye ◽  
Michel R. Langlois
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Subclinical Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
Ldl Particles ◽  
Subendothelial Space ◽  
Aged Subjects

AbstractLow-density lipoproteins (LDLs) are susceptible to structural modifications by oxidation, particularly the small dense LDL particles. The formation of lipid peroxidation derivates, such as thiobarbituric reactive substances, conjugated dienes, lipid hydroperoxides, and aldehydes, is associated with changes in apolipoprotein conformation and affects the functional properties of LDLs. Oxidized LDL (oxLDL) formation in the subendothelial space of the arterial wall is a key initiating step in atherosclerosis because it contributes to foam cell generation, endothelial dysfunction, and inflammatory processes. In the last decade, immunoassays were developed using monoclonal antibodies against oxidation-dependent epitopes of LDL which made it possible to directly measure oxLDL in the circulation. Increased circulating oxLDL concentrations have been related to cardiovascular disease in some studies, although not always independently after adjustment of classical lipid markers. The Asklepios Study, investigating 2524 healthy middle-aged subjects, showed that circulating oxLDL is affected by many biological and lifestyle factors, as well as (generalized) subclinical atherosclerosis.Clin Chem Lab Med 2009;47:128–37.

scholarly journals N-Acetylcysteine anAlliumPlant Compound Improves High-Sucrose Diet-Induced Obesity and Related Effects

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Gisele A. Souza ◽  
Geovana X. Ebaid ◽  
Fábio R. F. Seiva ◽  
Katiucha H. R. Rocha ◽  
Cristiano Machado Galhardi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Diet Induced Obesity ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

This study was designed to determine whetherN-acetylcysteine (NAC, C5H9–NO3S), a compound fromAlliumspecies may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance,in vivolow-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C,n= 6) and those receiving high-sucrose diet (HS,n= 18). After 22 days, (HS) group was divided into three groups (n= 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l−1-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l­1-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period) body weight, body mass index and surface area were enhanced in HS-HS rats (P< .001). HS-HS rats had glucose intolerance, increased serum triacylglycerol (TG), very low-density lipoprotein (VLDL), oxidized-LDL (ox-LDL) and lipid-hydroperoxide (LH) than the others (P< .01). NAC in HS-N and HS-CN rats reduced the obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P< .01) in these groups compared with HS-HS. Total antioxidant substances, GSH/GSSG ratio and glutathione-reductase, were higher in HS-N than in HS-HS (P< .01). In conclusion, NAC improved high-sucrose diet-induced obesity and its effects on glucose tolerance, lipid profile,in vivoLDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control.

scholarly journals Dynamic AFM detection of the oxidation-induced changes in size, stiffness, and stickiness of low-density lipoprotein

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kun Wang ◽  
Yuanfang Li ◽  
Chao Luo ◽  
Yong Chen
Keyword(s):  
Adhesion Force ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Biomechanical Properties ◽  
Ldl Oxidation ◽  
Low Density ◽  
Peripheral Tissues ◽  
Ldl Particles ◽  
Induced Changes

Abstract Background Low-density lipoprotein (LDL) is an important plasma lipoprotein transporting lipids to peripheral tissues/cells. The oxidation of LDL plays critical roles in atherogenesis and its oxidized form (oxLDL) is an important risk factor of atherosclerosis. The biomechanical properties of LDL/oxLDL are closely correlated with the disease. To date, however, the oxidation-induced changes in size and biomechanical properties (stiffness and stickiness) of LDL particles are less investigated. Methods In this study, copper-induced LDL oxidation was confirmed by detecting electrophoretic mobility, malondialdehyde production, and conjugated diene formation. Then, the topographical and biomechanical mappings of LDL particles before/after and during oxidation were performed by using atomic force microscopy (AFM) and the size and biomechanical forces of particles were measured and quantitatively analyzed. Results Oxidation induced a significant decrease in size and stiffness (Young’s modulus) but a significant increase in stickiness (adhesion force) of LDL particles. The smaller, softer, and stickier characteristics of oxidized LDL (oxLDL) partially explains its pro-atherosclerotic role. Conclusions The data implies that LDL oxidation probably aggravates atherogenesis by changing the size and biomechanical properties of LDL particles. The data may provide important information for a better understanding of LDL/oxLDL and atherosclerosis.

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

Effect of Turmeric and Ginger on Lipid Profile in Male Rats Exposed to Oxidative Stress

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Eman A. Al-Rekabi ◽  
Dheyaa K. Alomer ◽  
Rana Talib Al-Muswie ◽  
Khalid G. Al-Fartosi
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Drinking Water ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Male Rats ◽  
Control Group ◽  
Very Low Density Lipoprotein ◽  
Low Density

The present study aimed to investigate the effect of turmeric and ginger on lipid profile of male rats exposed to oxidative stress induced by hydrogen peroxide H2O2 at a concentration of 1% given with consumed drinking water to male rats. Methods: 200 mg/kg from turmeric and ginger were used, and the animals were treatment for 30 days. Results: the results showed a significant increase in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), whereas it explained a significant decrease in high density lipoprotein (HDL) of male rats exposed to oxidative stress when compared with control group. the results showed a significant decrease in cholesterol, triglycerides, (LDL), (VLDL), whereas it explained a significant increase in (HDL) of rats treated with turmeric and ginger at dose 200 mg/kg when compared with male rats exposed to oxidative stress.

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